{"doi":"10.1101/2025.04.22.649367","title":"Charting the transition from in vitro gliogenesis to the in vivo maturation of transplanted human glial progenitor cells","abstract":"Neither rodent models nor in vitro studies of human cells adequately describe the molecular ontogeny of human glial progenitor cells (hGPCs). Here, we used scRNA-seq together with scATAC-Seq and CUT&TAG assessment of chromatin availability to track the in vitro genesis and in vivo differentiation of hGPCs from pluripotent stem cells (PSCs). In vitro, the hGPC pool comprised 4 transcriptionally-distinct subpopulations, each associated with a distinct pattern of chromatin accessibility and histone modification of stage-dependent genes. After the neonatal transplant of these cells into myelin-deficient shiverer mice, they differentiated further as astrocytes and oligodendrocytes. A combination of gene co-expression, motif enrichment, cell-trajectory, and cell-cell interaction analyses revealed that the host environment potentiated the context-dependent differentiation of the hGPCs, via their activation of distinct gene regulatory networks. Together, these data chart the process by which human PSC-derived GPCs are generated in vitro and diversify in vivo to mature as astrocytes and oligodendrocytes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":557587,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6257,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1278284,"name":"Steven J. Schanz","orcid":"0000-0001-8359-5350","position":1,"is_corresponding":false},{"id":473396,"name":"Benjamin Mansky","orcid":"0000-0001-8652-0928","position":2,"is_corresponding":false},{"id":343007,"name":"Xiaolu Wei","orcid":"0000-0001-9952-3757","position":3,"is_corresponding":false},{"id":1457734,"name":"Carter C. Long","orcid":null,"position":4,"is_corresponding":false},{"id":886976,"name":"Devin Chandler-Militello","orcid":"0000-0002-3766-8368","position":5,"is_corresponding":false},{"id":251409,"name":"Nguyen P.T. Huynh","orcid":"0000-0002-7254-1645","position":6,"is_corresponding":false},{"id":304627,"name":"Steven A. Goldman","orcid":"0000-0002-5498-4303","position":7,"is_corresponding":false},{"id":886973,"name":"John N. Mariani","orcid":"0000-0002-0287-8461","position":0,"is_corresponding":true}],"reference_count":118,"raw_metadata":null,"created_at":"2026-07-19T02:55:17.435961Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}